Electrical impedance sensing has been used to measure biological materials, such as tissue samples and cell suspensions for over a hundred years. It has been used in bulk hemacytometers and flow cytometers extensively. The direct current (DC) resistive sensing extends to alternating current (AC) impedance sensing. At low AC frequency (under 100 kHz), the signal is determined mainly by the cell volume. At higher frequency (100 kHz to 10 MHz), the intracellular structures also contribute to the overall measured impedance and become explorable measurands.
A serious problem in AC impedance sensing of particles (e.g., blood cells in plasma) with micro electrodes is that with the shrinking of electrode surface area the electrode double layer capacitance decreases. The double layer capacitance is in series with the channel impedance to be measured and it dominates the system impedance in the low frequency range. In high frequency, the stray capacitance which is in parallel with the channel impedance becomes the dominant part in system impedance. Stray capacitance can arise from, non-ideal electrode to electrode isolation. In AC impedance sensing of particles, the measurement device is limited to a frequency range, which is high enough to bypass electrode double layer impedance and low enough that the stray capacitance does not play a significant role in overall system impedance. As the electrodes are reduced in size, the frequency range dominated by the double layer capacitance expands to higher frequency. As a result, the sensitivity for particle sensing decreases.
Conductivity sensing is a technique widely used in fields such as liquid chromatography (LC), capillary electrophoresis (CE), cytometry, and cell impedance analysis to analyze or detect the concentration or presence of the analytes of interest. It is often desirable to improve conductivity sensor sensitivity especially for the cases where the analytes concentrations are extremely low or the intrinsic sensor sensitivities are low due to design limitations. For example, the sensitivity of the capacitively-coupled contactless conductivity detector (C4D) is inferior to the conventional conductivity detector due to the fact that the sensing electrodes for C4D are covered by a protection layer and are not in direct contact with the electrolyte solution. While the C4D provides great advantages such as electrode robustness, the lower sensitivity certainly limits its application. It is often desirable to have a higher conductivity sensing sensitivity than can presently be attained, especially for the cases where the sensing electrodes are not in direct contact with the electrolyte solution. Therefore, there is a need to develop techniques that can enhance C4D sensitivity.